Development of a Numerical Model for Microbubble-Enhanced Treatment in HIFU Therapy High Intensity Focused Ultrasound (HIFU) is currently utilized in many modern therapeutic and surgical medical applications, such as for tissue ablation in the treatment of cancer and benign prostatic hyperplasia. New HIFU research frontier has moved toward the treatment of deep-seated solid tumors such as in liver and brain cancers because HIFU is the only truly noninvasive form of localized ablative therapy. To reduce undesirable pre-focal damage due to induced cavitation activity along the pathway, microbubbles used as ultrasonic contrast agents have been injected to the targeted region to promote heating by utilizing low intensity directed cavitation activity to the focal region. However, the behavior of microbubbles in a focused ultrasound field has not been fully investigated neither experimentally nor numerically due to the complex interactions between the oscillating bubbles and the ultrasound. In this SBIR effort we propose to develop a novel numerical approach to help accurately characterize the acoustic and thermal field with microbubble-enhanced ultrasound for different input characteristics. The numerical approach will employ Eulerian-Lagrangian coupled schemes in which the bubble dynamics are tracked in a Lagrangian fashion while the acoustic and thermal fields are resolved using a fixed grid Eulerian continuum approach. The heat deposition in the HIFU focal region contributed by both the ultrasound acoustic waves and the bubble oscillations will be modeled by solving heat transport equations. The two-way coupled approach allows to predict the nonlinear acoustic field and bubble behaviors accurately and accounts for both bubble-bubble and bubble-fluid interaction. A multi-level parallelization algorithm using both Graphic Processing Unit (GPU) and Central Processing Unit (CPU) computation technology will be implemented to speed up the computations. In Phase I the developed numerical model will be validated against well-documented experimental data available in the literature. In Phase II we will team up with Duke University to conduct ex vivo experiments using real tissue for further validation. The resulting computational tool can be used to help advance the research for microbubble-enhanced HIFU applications. In practice, the tool can be also utilized to explore a wide range of parameters to help selection of instrument setup, and to optimize the design and setting of the HIFU treatment so that higher safety and efficacy of treatments can be reached. The software will also be applicable to the modeling of other controlled cavitation bubbles such as those generated by shock wave lithotripter.